The present invention is related to a method for inhibiting cell growth intended for especially tumor cells, which is useful clinically and experimentally.
According to the vital statistics of Japan in 1994, the deceased number by cancer increases 7878 people from the previous year and is 244000 people. In this way, the deceased number by cancer has held the top spot since 1981 and occupies 28% of the total number of deaths. When the subjects are limited to the 50 from the 40 years old, the deceased number by cancer amounted to about one third of the total deceased number, and the number of cancer patients was 1327000 in the year of 1993. Recently, a variety of anticancer drugs and therapy have been developed, but the cancer is the big subject that still should be tackled.
The application the interferon has been tried to various cancers, in world every country heretofore. At present, the efficacy of interferon is seen in, for example, hairy cell leukemia, Kaposi sarcoma, chronic myeloid leukemia, non-Hodgkin""s lymphoma, multiple myeloma, malignant melanoma, and renal cell carcinoma (Tyringt et al., xe2x80x9cInterferonxe2x80x9d pp. 399-308, edited by Baron et al.).
The application of the various kinds of interferon such as interferon-xcex1, interferon-xcex2 and interferon-xcex3 as the anticancer drug were tried by as many as 18 research groups, under the guidance of the Ministry of Health and Welfare xe2x80x9cthe Special Research regarding the Clinical application of Interferonxe2x80x9d from the latter half of the 1970""s even in Japan.
About these results, according to the report of Ohno (xe2x80x9cGan To Kagakuryohoxe2x80x9d, vol. 14, No. 5, pp. 1194-1202, 1987), the efficacy to the renal cell cancer is 6-23% with interferon-xcex1 and 4-20% with interferon-xcex2; to the brain tumor in systemic administration is 4-20% with interferon-xcex1 and 13-17% with interferon-xcex2; to the multiple myeloma is 0-30% with interferon-xcex1 and 4-25% with interferon-xcex2; to the skin cancer in local administration is 48-72% with interferon-xcex1 and 33-53% with interferon-xcex2. The approval of the application of these drugs has been obtained on the basis of these results. Additionally, interferon is also effective to hematopoietic tumors. Especially, interferon-xcex1 is effective to chronic lymphocytic leukemia in 3 cases of 19 cases; is effective to chronic myeloid leukemia in 4 cases of 14 cases; and is effective to hairy cell leukemia in 2 cases of 3 cases.
Unlike these results, the efficacy which is 0-6% to the solid tumor such as mammary carcinoma, stomach cancer and hepatocellular carcinoma has been hardly admitted.
Since interferon is certainly effective to renal cell cancer and hairy cell leukemia, which are not sensitive to the other anticancer drugs and exhibits some effects on multiple myeloma and malignant lymphoma on which the other drugs are ineffective, the efficacy of interferon is admitted. However, the results are still not satisfactory, since the interferon have almost no efficacy on solid tumors and the efficacy thereof is still around 20%, except the local administration of the drugs to skin cancer.
Efficacy of the interferon as therapeutic drugs for hepatitis B and hepatitis C is also approved based on antiviral actions thereof, as well as the applications based on antitumor effect thereof. It is known that hepatitis C causes chronic hepatitis and progress to liver cirrhosis, hepatocellular carcinoma in succession. It has been clarified that 80 percent of hepatocellular carcinoma occurs based on chronic hepatic diseases caused by the hepatitis C virus. The interferon has anti-viral activities to these hepatitis C viruses and allow the patients to be free from the virus and allow transaminase to be normal, and have become the first choice of therapy of hepatitis C (Ikegami et al., xe2x80x9cIgaku No Ayumixe2x80x9d, vol. 181, No. 5, pp. 341-344, 1997).
However, recent reports show that the effects of interferon are greatly affected by the amount of hepatitis C virus, that is, efficacy cannot be significantly obtained in hepatitis C patients with a large amount of the virus. Accordingly, how to improve the efficacy for these patients therefore becomes a big subject (Yatsuhashi et al., xe2x80x9cIgaku No Ayumixe2x80x9d, vol. 181, No. 5, pp. 333-336, 1997).
Okushin et al. indicated the possibility of a new approach to these problems (xe2x80x9cKanzoxe2x80x9d, vol. 36, pp. 735, 1995: and xe2x80x9cKanzoxe2x80x9d, vol. 38, No. 1, 1997). Specifically, they found that therapeutic results for hepatitis C patients that are not effective for conventional therapies can be markedly improved when an interferon-xcex2 is administered to such hepatitis C patients twice a day while a daily dose is divided into two doses per day.
The twice-a-day administration increases the effects to the virus replication, and additionally, increases antitumor activities, as reported by Tanahashi et al. (xe2x80x9cGan To Kagakuryohoxe2x80x9d, vol. 14, No. 4, pp. 1156-1159, 1987) and Niijima et al. (Cancer Immunology, Immunotherapy, vol. 30, No. 2, pp. 81-85, 1989). Namely, they administered a genetically recombinant human interferon-xcex2 to the urinary bladder cavity of patients with superficial bladder tumor at a dose of 3600xc3x97104 once a day or at a dose of 1800xc3x97104 twice a day, and evaluated the antitumor effects of the administration. Consequently, a higher efficacy can be obtained in the administration at a dose of 1800xc3x97104 twice a day than in the administration at a dose of 3600xc3x97104 once a day.
As described above, the reports on antiviral action or antitumor action show that the efficacy becomes higher in the administration of an interferon twice a day than in the administration in the same amount once a day. Although the mechanisms of antiviral and anti-tumor action of interferon have not been clarified yet, it is speculated that the antiviral action and anti-tumor action act under different mechanisms from each other, (Gewert et al., xe2x80x9cInterferonxe2x80x9d, pp. 289-297, edited by Baron et al.; Fleischmann et al., xe2x80x9cInterferonxe2x80x9d, pp. 299-309, 1992, edited by Baron et al.).
Since the effects on the anti-tumor activity have been obtained at a very high dose of 1800xc3x97104 units per dose per day and have been obtained with local administration, the effects with systemic administration such as intravenous administration have not been clarified yet. In particular, it is known that such interferon rapidly disappears from the blood circulation when they are intravenously administered (Satoh et al., xe2x80x9cJ. Interferon Resxe2x80x9d, vol. 4, No. 3, pp. 411-422, 1984).
As mentioned above, since the sufficient therapy or drug therapy have not been established yet in treatment of disease based on the abnormal proliferation of the cell, especially cancer, the establishment of the novel therapy and also drug therapy are hoped from now on.
Accordingly, an object of the present invention is to provide an industrially and medically useful novel method for inhibiting cell growth, which is directed to the therapy of cancers and of diseases occurred under a similar action mechanism, on which the interferon have not yet exhibited sufficient therapeutic effects.
The present invention provides a method for inhibiting cell growth, which includes the step of systemically administering a pharmaceutical preparation containing an interferon as an active ingredient two or more times a day.